BETHESDA, MD — Poly ADP-ribose polymerase inhibitors (PARPis) are an important class of therapeutics for metastatic castration-resistant prostate cancer (mCRPC),
Unlike hormone-based treatments for mCRPC, however, PARPis are not without drug-related hematological adverse events, according to a new review.
A study led by researchers from the Uniformed Services University of the Health Sciences and including participation from the Murtha Cancer Center Research Program, the
Henry M Jackson Foundation for the Advancement of Military Medicine Inc. and the Walter Reed National Medical Center, all in Bethesda, MD, sought to review the evidence on hematological toxicities, including anemia, thrombocytopenia and neutropenia from PARPis in prostate cancer.
The study team performed a systematic review and meta-analysis using the PRISMA guidelines for phase II and III randomized controlled trials (RCTs) of PARPis in prostate cancer. The researchers queried PubMed, Embase and Ovid All EBM reviews-Cochrane inception to June 9, 2023. The Mantel-Haenszel method was used to report risk ratios (RR) and 95% confidence intervals (CI) for all-grade and high-grade anemia, thrombocytopenia, and neutropenia toxicities. The results were published in the journal Cancers (Basel).1
The systematic review retrieved eight phase II and III RCTs; with eight included in the anemia area, five in the all-grade thrombocytopenia and neutropenia, and four in the high-grade thrombocytopenia and neutropenia outcomes.
Results indicated that, compared to a placebo and/or other non-PARPi treatments, PARPi use was associated with an increased risk of:
- all-grade anemia (RR, 3.37; 95% CI, 2.37-4.79; p < 0.00001),
- thrombocytopenia (RR, 4.54; 95% CI, 1.97-10.44; p = 0.0004), and
- neutropenia (RR, 3.11; 95% CI, 1.60-6.03; p = 0.0008).
“High-grade anemia (RR, 6.94; 95% CI, 4.06-11.86; p < 0.00001) and thrombocytopenia (RR, 5.52; 95% CI, 2.80-10.88; p < 0.00001) were also associated with an increased risk, while high-grade neutropenia (RR, 3.63; 95% CI, 0.77-17.23; p = 0.10) showed no significant association,” the authors pointed out. “Subgroup stratification analyses showed differences in various all-grade and high-grade toxicities.”
The researchers suggested that “future studies with more pooled RCTs will enhance this understanding and continue to inform patient-physician shared decision-making. Future studies may also have a role in improving the current management strategies for these AEs.”
- Bowling GC, Swargaloganathan P, Heintz C, Madan RA, et. al. Hematological Toxicities with PARP Inhibitors in Prostate Cancer: A Systematic Review and Meta-Analysis of Phase II/III Randomized Controlled Trials. Cancers (Basel). 2023 Oct 9;15(19):4904. doi: 10.3390/cancers15194904. PMID: 37835597; PMCID: PMC10571760.